14.5% of Australian adults smoke cigarettes – this is down from 22.4% at the turn of the century. The rates are similar in the US but much higher across Europe – with an average closer to 30%.

There’s pretty much nothing we can do for a smoking patient that would improve their health as much as getting them to quit smoking would. So how do we do it? Firstly, are you more likely to quit successfully if you stop it “cold turkey”, or is it better to stop gradually? Secondly, can medications help? and by how much?

This week we look at a randomised controlled trial that compared gradual smoking cessation to abrupt cessation. We’ll then examine the evidence for each of the different pharmacological treatments used to help people quit.

Etymology of “Cold Turkey”

Given that it’s almost universally used to depict the sudden stopping an addiction suddenly, where in the world did this term come from?

According to the Online Etymology Dictionary, it came from the fact that cold turkey is a dish that doesn’t require much preparation. So quitting “cold turkey”, is quitting suddenly or without any preparation. But then dictionary.com reports it’s origin comes from a common phrase used in America in the 1950’s: “to talk turkey” which means to speak bluntly about something. …if only there was a peer-reviewed journal of etymology.

Benefits of quitting smoking

I think we are all sold on the benefits of quitting smoking, but it’s worth mentioning one particular trial just to remind us. It was published in Chest in 2007 and the brilliance of this trial was that they were assessing the outcomes of a smoking cessation intervention, rather than whether they actually quit or not. Normally studies will tell us, say, the cardiovascular disease reduction in a group of people who quit smoking versus those who continued smoking. But this study just assessed the cardiovascular outcomes from whether you gave an intervention to help people stop smoking or whether you didn’, regardless of how many actually quit in each group.

They recruited 209 smokers who had just been admitted to hospital for either heart failure or a heart attack. Everyone got about half an hour of counselling about the harms of smoking and how to quit and were given a lot of written information prior to discharge from hospital. They were then randomised into two groups: An intensive treatment group who got a further 12 weeks of counselling plus pharmacological therapy to help them quit like nicotine replacement therapy or bupropion. The second group was a usual care group who didn’t get further intervention outside of that 30 minute counselling session in hospital.

At the end of 2 years, the mortality rate was 12% in the usual care group, but in the intensive smoking cessation group it was only 2.8%. So a 10% absolute reduction in all-cause mortality after 2 years just by providing an intervention to help patients quit. This is unheard of for any other intervention. Let’s compare it to aspirin for example, because no doctor in the world would not be firm about taking aspirin after a heart attack (unless they couldn’t take it for whatever reason). But giving aspirin for 2 years after a heart attack leads to a 1.4% reduction in mortality. So this 10% is huge.

What’s encouraging to me, is that the rates of smoking cessation at 2 years were not fantastic. 9% in the usual care group and 33% in the intensive treatment group. So it’s nice to know that even if the majority of patients are not quitting despite your constant nagging, overall, it’s still providing a very impressive benefit.

Cold Turkey Versus Gradual Quitting

A good quality randomised controlled trial has been conducted to see whether gradual smoking cessation is more or less effective than cold turkey. It was published in the Annals of Internal Medicine in May 2016.

They took 697 adult smokers who were smoking at least 15 cigarettes per day and were addicted. They made sure they were addicted by conducting a survey called the Fagestrom Test for Nicotine Dependence (FTND), which asks things like: how soon after waking do you have your first cigarette, do you find it hard to refrain from smoking in places it’s forbidden like a library or church, and do you smoke even if you’re so sick, that you stay bed the whole day? It’s a score out of 10, where a score above 5 is considered moderately dependant.

They were randomised into 2 groups: All of the participants in both groups were told to set a quit date for 2 weeks time. The cold turkey group were told to smoke as normal and not reduce the number of cigarettes they smoked until that quit date. The gradual cessation group were told to aim to half the number of cigarettes they smoked in the first week, then half them again in the second week and then quit after the second week. The second group were given nicotine replacement therapy during those 2 weeks as they were reducing their cigarettes. They could get either nicotine gum, nasal spray, mouth spray, lozenges, inhalers, or sublingual tablets.

Both groups received counselling and support during the 2 weeks before the quit date.

They followed them up for 6 months and the primary outcome was how many were abstinent from cigarettes after 4 weeks. They confirmed abstinence by using a tool called the Russell Standard, which incorporates exhaled carbon monoxide concentrations to confirm abstinence. They also did this at 8 weeks and 6 months.

Results

The average age of the patients was 49, half of them were men, and they were smoking an average of 20 cigarettes per day. The average FTND addiction score was 6 indicating that they were moderately addicted. 94% were white.

At 4 weeks, abstinence was achieved in 39% of those in the gradual cessation group, but in the cold turkey group, this increased to 49%. So a 10% absolute reduction in smoking rates making a number needed to treat of 10 in favour of cold turkey quitting.

By 6 months, as you’d expect with these things, the rates of abstinence were much lower – but they were still better for the cold turkey quitters. They were 15.5% in the gradual cessation group versus 22% in the cold turkey group. making a number needed to treat of 16.

They asked all the patients at the start of the study whether they would prefer gradual or sudden smoking cessation. Interestingly, of those who preferred gradual cessation, they were still more likely to quit when they stopped abruptly compared to if they stopped gradually.

Pharmacological treatment of smoking addiction

There are 4 agents that have good evidence to improve smoking cessation rates in smokers who are willing to quit. They are: Nicotine Replacement Therapy (NRT), nortriptyline, bupropion and varenicline (Champix or Chantix)

Nicotine Replacement Therapy

There ’s been a Cochrane review on this. In fact, there’s a Cochrane review for each of these 4 medications.

Firstly, what would you predict the actual quit rate is for someone who is motivated to quit? (i.e.they’re in the “action” phase of that Prochaska-Diclemente cycle of change).

It’s around 10%! And this was consistent among all the placebo arms in all of these Cochrane reviews. It just shows how addictive these things are. Mark Twain wrote: “giving up smoking is easy, I’ve done hundreds of times”

The Cochrane review was able to find 117 RCT’s making up over 50,000 patients assessing the benefits of nicotine replacement therapy.

In the no intervention group, 10% were able to achieve abstinence and this went up to 16% in the NRT group. And it didn’t seem to matter which NRT you used whether it was gum, patches, inhalers, sprays or lozenges.

They had some really great analyses in the review, here are the highlights:

In studies that compared short duration of nicotine replacement therapy versus longer duration – there was no difference in abstinence rates. The authors of the Cochrane review recommend 8 weeks.

Using a combination of a long-acting NRT like a patch, together with a short-acting NRT, like gum, spray or inhalers (to control sudden cravings), seem to be better than either one alone. It was about 15% abstinence with just a long acting or short acting, versus 20% when using a combination of both.

There was a slight benefit to starting the nicotine replacement therapy before the actual quit date rather than starting after.

The harms of NRT seemed to be local reactions like skin irritation from the patch, hiccups and sore throat in the mouth spray, and bad taste with the gum. They couldn’t find any increase in cardiovascular disease but they did find an increase in palpitations or chest pain which occurred in 1.4% of the placebo group versus 2.6% in the NRT group.

Bupropion

The Cochrane review that looked into the efficacy of bupropion for smoking cessation found 44 RCT’s with 13,700 patients

The abstinence rate in the placebo group was 11.5% and this went up to 18.7% with bupropion. So very similar to nicotine replacement therapy. In fact in the hand full of trials that directly compared bupropion to nicotine replacement therapy there was no difference in effectiveness. The main side effects with bupropion are insomnia, which occurring in 25% compared to 15% in placebo; dry mouth and nausea. More alarmingly, it does increase seizures but this is very rare, in the order of 1 in 1000, but obviously wouldn’t want to give it anyone with epilepsy.

Nortriptyline

This Cochrane review found 11 studies making up 2 and a half thousand patients, and showed very similar results to the others – 10% abstinence rates for placebo versus 20% for nortriptyline. In the trials that compared it to nicotine replacement therapy it was maybe slightly better but not statistically significant.

In terms of side effects, they are mainly the anticholinergic side effects like sedation, dry mouth, constipation, difficulty urinating and blurred vision. The main fear with the tricyclic antidepressants is their often fatal in overdose so I you’d need to be confident the patient doesn’t have any risk of suicidality.

Varenicline (Champix)

This Cochrane review found 27 RCT’s making up around 12 thousand patients. Those who attempted to quit smoking with placebo had an 11% chance of remaining abstinent in these trials. But if they quit using varenicline, this went up to 25%.

There have also been studies comparing varenicline to some of the other smoking cessation medications:

8 trials compared varenicline to nicotine replacement therapy – For NRT abstinence was achieved in 19% versus 23.7% with varenicline. So the chance of successfully quitting was 4% higher with varenicline over nicotine replacement therapy.

5 trials compared varenicline to bupropion finding varenicline to be superior by about 6.5% – it was 17% versus 24%.

In terms of adverse effects, the major concern has been about neuropsychiatric harms: things like depression, suicide, strange behaviours, anger and things like that. In fact, in 2009, the FDA put a black box warning on Champix with regards to these adverse events. But in 2015 a large meta analysis specifically looking at these side effects was published in the BMJ and with 39 RCT’s, found no difference in depression, suicide ideation, attempted suicide, aggressive behaviours or irritability. Since then there has also been a large, good quality trial with 8000 patients of which 4000 had a psychiatric disorder, and the main aim of the study was to detect any neuropsychiatric effects. This was called the EAGLES study and they also couldn’t find any increase in psychiatric issues with varenicline. The harms they could find were: nausea occurring in 25% of people, abnormal dreams occurring in about 12%, more fatigue and insomnia as well.

Bottom Line

Cold turkey seems to be a better approach to smoking cessation achieving a 10% increase in abstinence rates at 4 weeks over gradual cessation. The chance of achieving abstinence in a motivated person without any help is about 10%, and this can be doubled with either nicotine replacement therapy, bupropion, nortriptyline or varenicline (Champix). Champix seems superior to the other methods achieving a 4-6% improvement in abstinence over NRT and bupropion.